Staphylococcal enterotoxin B (SEB;Category B agent), a toxin that commonly causes classic food poisoning and can cause a nonmenstrual toxic shock syndrome (TSS), is a potential biological warfare agent. Importantly, SEB is derived from common readily accessible bacteria, is relatively easily produced, and can be delivered in a stable aerosol form. An SEB attack would be devastating to civilian populations as well as on the battlefield during times of war. Currently, there are no preventatives or therapeutics available against SEB. Monoclonal antibodies (Mabs) are a class of FDA-approved therapeutics shown to neutralize toxins. Because of their specificity, stability, high potency, and versatility human Mabs are ideal for biodefense related countermeasures. The Product Development Goals of this NIAID-AT-SBIR proposal are to: (1) generate a panel of fully human anti-SEB Mabs;(2) select lead anti-SEB Mabs based upon prophylactic efficacy in mouse intoxication models;(3) compare the protective efficacy of the lead Mabs when expressed in mammalian cell culture with the identical Mab expressed in a rapid, highly scalable manufacturing system. The Long Range Objective is to develop a safe and effective immunoprotectant product for SEB. Two product modalities are envisioned: 1) A preventive product consisting of a human anti-SEB Mab for intramuscular administration prior to potential exposure to weaponized SEB. 2) A therapeutic product consisting of the human anti-SEB Mabs administered in combination with Mab(s) against pro-inflammatory cytokines to provide protection post- exposure. Experiments addressing this application will be performed in a subsequent Phase 2 proposal. PUBLIC HEALTH RELEVANCE: Staphylococcal enterotoxin B (SEB;Category B agent), a toxin that commonly causes classic food poisoning and can cause a nonmenstrual toxic shock syndrome (TSS), is a potential biological warfare agent. Importantly, SEB is derived from common readily accessible bacteria, is relatively easily produced, and can be delivered in a stable aerosol form. Currently, there are no preventatives or therapeutics available against SEB. Mapp Biopharmaceutical's R&D team proposes to develop a novel, safe, low cost immunoprotectant for preventing and treating SEB intoxication.